Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen, Germany.
Nat Rev Rheumatol. 2010 Oct;6(10):589-98. doi: 10.1038/nrrheum.2010.141. Epub 2010 Sep 7.
Cyclo-oxygenase (COX) inhibitors are widely used to relieve musculoskeletal pain. These agents block the production of prostaglandins (PGs) at sites of inflammation by inhibiting the activity of two COX enzymes necessary for PG production and normal organ homeostasis. Inhibition of PG production at sites unrelated to pain is associated with adverse drug reactions (ADRs). The degree of analgesic efficacy, as well as the incidence and the localization of ADRs, are critically influenced by the pharmacokinetics (absorption, distribution and elimination) of these drugs. Ideally, sufficient and permanent inhibition of COX enzymes should be achieved in target tissues, with minimal ADRs. To minimize underdosing or overdosing, which result in therapeutic failure or ADRs, the COX inhibitor with the most appropriate pharmacokinetic properties should be selected on the basis of a thorough pharmacokinetic-pharmacodynamic analysis. In this Review, the pharmacokinetics of the prevailing COX inhibitors will be discussed and enigmatic aspects of these intensively used drugs will be considered.
环氧化酶 (COX) 抑制剂被广泛用于缓解肌肉骨骼疼痛。这些药物通过抑制前列腺素 (PG) 生成所必需的两种 COX 酶的活性，在炎症部位阻断 PG 的产生，从而维持正常器官的内稳态。在与疼痛无关的部位抑制 PG 的产生与药物不良反应 (ADR) 有关。这些药物的药代动力学（吸收、分布和消除）对其镇痛效果的程度、ADR 的发生率和定位具有重要影响。理想情况下，在目标组织中应实现 COX 酶的充分和持久抑制，同时最小化 ADR。为了最小化治疗失败或 ADR 导致的剂量不足或过量，应根据全面的药代动力学-药效学分析选择具有最合适药代动力学特性的 COX 抑制剂。在这篇综述中，将讨论目前 COX 抑制剂的药代动力学，并考虑这些广泛使用的药物的一些复杂方面。
